NM_001267550.2(TTN):c.25223C>T (p.Thr8408Ile) AND not specified

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Apr 9, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000040024.25

Allele description [Variation Report for NM_001267550.2(TTN):c.25223C>T (p.Thr8408Ile)]

NM_001267550.2(TTN):c.25223C>T (p.Thr8408Ile)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.25223C>T (p.Thr8408Ile)

HGVS:

NC_000002.12:g.178717651G>A
NG_011618.3:g.118152C>T
NM_001256850.1:c.24272C>T
NM_001267550.2:c.25223C>TMANE SELECT
NM_003319.4:c.13282+20431C>T
NM_133378.4:c.21491C>T
NM_133432.3:c.13657+20431C>T
NM_133437.4:c.13858+20431C>T
NP_001243779.1:p.Thr8091Ile
NP_001254479.2:p.Thr8408Ile
NP_596869.4:p.Thr7164Ile
NP_596869.4:p.Thr7164Ile
LRG_391t1:c.25223C>T
LRG_391:g.118152C>T
NC_000002.11:g.179582378G>A
NM_001267550.1:c.25223C>T
c.21491C>T

Protein change:

T7164I

Links:

dbSNP: rs201432372

NCBI 1000 Genomes Browser:

rs201432372

Molecular consequence:

NM_003319.4:c.13282+20431C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+20431C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+20431C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.24272C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.25223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.21491C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000063715	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Oct 22, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000114357	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Aug 21, 2015)	germline	clinical testing	Citation Link,
SCV000616033	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Oct 28, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001978802	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV006068736	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Apr 9, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	3	3	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000063715.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

Description

p.Thr7164Ile in exon 84 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (27/9550) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs201432372).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	3	not provided

From Eurofins Ntd Llc (ga), SCV000114357.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From Athena Diagnostics, SCV000616033.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001978802.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV006068736.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

BS1;BP1;BP6

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 14, 2025

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